SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Butamirate 7.5mg/5ml Syrup

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml of syrup contains 1.5 mg butamirate citrate equivalent to 0.924 mg butamirate. 5 ml of syrup contains 7.5 mg butamirate citrate equivalent to 4.62 mg butamirate.

Excipient with known effect:

1 ml of oral suspension contains 450 mg of sorbitol.

1 ml of oral suspension contains 125 mg of glycerol.

5 ml of oral suspension contains 2250 mg of sorbitol.

5 ml of oral suspension contains 625 mg of glycerol.

For the full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Syrup

Colourless or pale yellow liquid.

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic treatment of non-productive cough.

4.2 Posology and method of administration

Posology

Adults

Recommended dose - 15 ml up to 4 times daily Treatment is limited to the symptomatic period.

Medical advice should be sought if the cough lasts longer than 4-5 days or if fever, dyspnoea or chest pain develops.

Patients with renal or hepatic impairment

Data is lacking in patients with impaired renal or hepatic function. Patients with renal and/or liver disease may be at greater risk for adverse effects from butamirate due to drug and metabolite accumulation.

Method of administration

Butamirate syrup should be taken orally.

4.3 Contraindications

-    Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

-    Children and adolescents under 18 years of age.

4.4 Special warnings and precautions for use

Before prescribing an antitussive treatment, the causes of the cough should be investigated to assess the need for aetiological treatment. If the cough persists after taking the antitussive treatment at the usual dose, the dose should not be increased; instead, the clinical situation should be reviewed.

Antitussives should not be used for prolonged periods.

Due to inhibition of the cough reflex by butamirate, the concomitant administration of expectorants must be avoided because this can lead to the stagnation of mucus in the respiratory tract, increasing the risk of bronchospasm and respiratory tract infections.

This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

None known.

The effects of other medicinal products on butamirate pharmacokinetics have not been investigated. Butamirate should not be used together with strong enzyme inhibitors, due to the possible risk of increased exposure of butamirate.

There is no knowledge about the potential of butamirate to affect plasma concentrations of other drugs. Therefore, medicinal products with a narrow therapeutic index should not be used together with butamirate, due to the possible risk of altered exposure to these drugs.

4.6 Fertility, pregnancy and lactation

Pregnancy

No studies have been conducted in pregnant women; therefore butamirate should not be used in the first trimester of pregnancy. During the second and third trimesters of pregnancy, butamirate should be administered with caution and only if absolutely necessary, taking into consideration the benefit for the mother and the potential risk for the foetus.

Breastfeeding

Since there are no data available on the excretion of the active substance or its metabolites in breast milk, the use of butamirate during breast-feeding is not recommended.

Fertility

No data available.

4.7 Effects on ability to drive and use machines

Butamirate may cause drowsiness and dizziness. Therefore, this medicinal product should be used with caution in drivers and individuals using machines.

4.8 Undesirable effects

Nervous system disorders

Rare (>1/10,000,<1/1,000): drowsiness, dizziness

Gastrointestinal disorders

Rare (>1/10,000,<1/1,000): nausea, diarrhoea

Skin and subcutaneous tissue disorders

Rare (>1/10,000,<1/1,000): urticaria

Immune system disorders:

Frequency not known: hypersensitivity reactions

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme

Website: www.mhra.gov .uk/yellowcard

4.9 Overdose

Symptoms

Butamirate overdose may lead to the following symptoms: drowsiness, nausea, vomiting, diarrhoea, dizziness, hypotension.

Measures

The following standard treatment is recommended: gastric lavage, administration of activated charcoal and, if necessary, the monitoring and treatment of vital signs. There is no known specific antidote.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other cough suppressants, ATC code: R05DB13

Butamirate syrup contains butamirate citrate which is a cough suppressant used for the symptomatic treatment of non-productive cough.

Butamirate acts centrally by diminishing the tussigenic reflex, and also acts peripherally via a bronchospasmolytic activity enhanced by an anti-inflammatory action.

Butamirate is a non-narcotic substance that is not chemically or pharmacologically related to the opioid alkaloids. It does not produce the undesirable effects caused by narcotic antitussives, such as sedation, constipation and addiction.

Butamirate is well tolerated and suitable for cough relief in adults.

5.2 Pharmacokinetic properties

Butamirate administered orally is absorbed rapidly and completely. The peak plasma level of the principal metabolite, 2-phenylbutyric acid, is 6.4 pg/mL following administration of 150 mg butamirate citrate in syrup form, and is reached in approximately 1.5 hours. The apparent elimination half-life is approximately 6 hours. The behaviour is linear following repeat administration; no accumulation is observed.

Hydrolysis of butamirate, principally in 2-phenylbutyric acid and diethylaminoethoxyethanol, begins in the plasma. These two metabolites also have an antitussive action and are, like butamirate, extensively bound to plasma proteins (approximately 95%), which accounts for the long plasma half-life. 2-phenylbutyric acid is partially metabolised by hydroxylation in the para position. The three metabolites are mainly eliminated renally, with the acid metabolites being extensively linked to glucuronic acid.

5.3 Preclinical safety data

No data available.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sorbitol (E420)

Glycerol Sucralose (E955)

Sodium benzoate (E211)

Citric acid monohydrate

Caramel flavour 12788 containing: flavouring substances flavouring preparations natural flavouring substances propylene glycol (E1520)

Mix Chocolate 70244 containing:

flavouring preparations flavouring substances natural flavouring substances smoke flavourings propylene glycol (E1520) water

quinine hydrochloride

dextrose

quassin

Purified water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

Shelf life after first opening the bottle: 6 months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Butamirate syrup is supplied in a 100 ml or 200 ml amber glass or polyethylene terephthalate bottle with a child-resistant polypropylene / polyethylene screw cap.

Each pack contains a polypropylene measuring cup graduated for dosing of 5 ml, 10 ml, 15 ml, 20 ml, 25 ml and 30 ml.

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material from it should be disposed of in accordance with local requirements.

MARKETING AUTHORISATION HOLDER

Actavis Group PTC ehf.

Reykjavikurvegi 76-78 220 Hafnarfjordur Iceland

30/04/2015